Phenylketonuria, a hereditary disease resulting in high phenylalanine blood levels causes mental retardation in children. In phenylketonuric mothers it may cause cerebral injury to the genetically unaffected fetus. Two phenylalanine degrading enzymes: phenylalanine ammonia lyase (PAL) and phenylalanine hydroxylase are purified and immobilized to hollow fibers. Cartridges constructed from these fibers will be studied in vitro for kinetic behavior and stability and in vivo in dogs and monkeys for physiologic and particularly hematologic effects as well as ability to lower high, induced phenylalanine levels. Hematologic problems encountered in preliminary experiments will be approached by insolubilizing activators of the fibrinolysin system (streptokinase, urokinase) onto the hollow fibers in order to prevent local blood coagulation. In preliminary experiments this appeared to be successful. It is hoped that acceptable, therapeutically useful reactors can be developed in these studies for the prevention of phenylketonuria induced mental retardation.